Primate erythrocytes (E) appear to serve as a first defense for removing potentially pathogenic immune complexes (IC) from the circulation. Primate E intercept IC via complement receptors (CRl). DRl bind C3b and possibly C4b sites generated on IC during activation of the complement cascade. IC bound to E are efficiently removed for the E as it traverses the liver. The E itself is immediately returned to the circulation. In addition to acting as a transport system for carrying IC to the liver, E-CRl also serve as a cofactor in the Factor I-mediated cleavage of C3b, thereby reducing the phlogistic potential of IC. patients with Acquired Immune Deficiency Syndrome (AIDS), as well as patients with a variety of other diseases, have reduced numbers of E-CRl. This raises the possibility that inadequate clearance of IC from the circulation, due to reduced expression of E-CRl, may explain some of the clinical manifestations of AIDS and perhaps other diseases. How the immunochemical properties of IC affect their interactions with E is poorly understood, partly as the result of the inherent heterogeneity of polyclonal IC used previously in most studies of E-IC interactions. To precisely analyze how the immunochemical properties of IC influence IC binding to E, we have begun to construct a panel of model IC using monoclonal antibodies. We have recently reported that, in baboons, a model IC probe that bound relatively poorly to E was preferentially deposited in glomeruli. We have used these probes to reveal defects in the interactions between IC and E from patients with IC disease. We have discovered that there are striking differences ln the binding of IC of differing antibody isotypes to E. Experiments presented in this proposal are designed to further analyze how the immunochemical properties of IC affect both IC binding to and release from human E. It is the principal long-term goal of this study to determine some of the major properties of IC that influence their interactions with E, using well-defined IC probes.